Water-in-oil-in-water double emulsions are systems in which a water-in-oil (W/O) emulsion is dispersed in a second aqueous phase. The W/O emulsion exists in the suspending aqueous medium as oil globules containing smaller water droplets. Preparation of W/O/W emulsions requires an emulsifying system with an intermediate HLB (hydrophilic-lipophilic balance) value. A W/O emulsion is first prepared using a lipophilic emulsifier such as SPAN® 85, while during the second step, the W/O emulsion was mixed with an aqueous solution of a hydrophilic emulsifier such as TWEEN® 80 to provide W/O/W emulsions. Two key challenges in vaccine development are related to developing formulations that do not require refrigeration and finding an absorbable adjuvant in vivo. The former maintains and preserves the quality of a vaccine before it is administered, and the latter is critical to evading hypersensitive reactions after vaccine administration.
U.S. Pat. No. 8,444,993 discloses a W/O/W emulsion comprising SPAN® 85 and poly(ethylene glycol)-block-poly(lactide-co-ε-caprolactone) (PEG-b-PLACL) as an emulsifying agent. That emulsion system exhibited a controlled release of antigen similar to SPAN/TWEEN emulsion. However for a W/O/W emulsion, having the same controlled release effect does not translate into having the same emulsion-stabilizing effect (see FIGS. 6C and 6D). Moreover, it has been well documented that the traditional emulsifiers TWEEN®, SPAN® and poloxamers may cause toxicities including severe nonimmunological anaphylactoid reactions.
A heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies, especially in connection with formulations of W/O/W emulsions that are biodegradable without using sorbitan esters and their ethoxylates (SPAN® and TWEEN®), or poloxamers.